Infectious pathogens including bacteria, mycobacteria, fungi, viruses and protozoa are known to cause a wide variety of recognizable ocular infections that can be diagnosed clinically and treated with specific antibiotic therapy. Typically infectious ocular diseases are characterized by an inflammatory response to rid the host of the offending microorganism. There are several ocular conditions including neoplastic, degenerative and autoimmune diseases in which routine clinical investigations reveal no direct evidence of a causative infectious pathogen. Our group is interested in investigating the role of infectious pathogens in the pathogenesis of ocular diseases that may lead to better diagnostic methods and treatment strategies. In ongoing clinical studies our group continues to investigate the etiology of Human T cell Lymphotrophic Virus, Type 1 (HTLV-1) keratopathy which we reported last year. Elevated serum immunoglobulin levels were found in all of the index cases of HTLV-1 keratopathy. Examination of cohort of patients with HTLV-1 associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma (ATL) showed that elevated serum immunoglobulin levels were associated with HTLV-1 keratopathy and that HTLV-1 keratopathy was more likely in patients with ATL. In a clinicopathologic study of a postmortem globe we demonstrated that ATL can present in the eye as a necrotizing vasculitis. Additionally, in conjunctival biopsies of patients with ATL we found that expression of T cell chemokines by conjunctival resident cells may contribute to the pattern of invasion of the infiltrating lymphoma cells. A pediatric patient with chronic granulomatous disease (CGD) and a history of recurrent bacterial infections presented with a chorioretinal mass suspicious for a choroidal granuloma, intraocular abscess or an intraocular neoplasm. The study of a chorioretinal biopsy specimen, however, revealed an unusual proliferation of smooth muscle cells and fibrous tissue with chronic inflammation without evidence of infectious organisms. This finding expands the spectrum of the ophthalmic manifestations of CGD. Finally, this year we continued to exploit the power of the polymerase chain reaction technique combined with microdissection to diagnose a case of culture negative Propionibacterium Acnes endophthalmitis. This case further demonstrates the utility of this technology to diagnose ocular disease induced by infectious agents and with appropriate treatment prevent ocular morbidity.